Abstract
Recent advances in additive manufacturing (AM) technologies provide tools to fabricate biological structures with complex three-dimensional (3D) organization. Deposition-based approaches have been exploited to manufacture multimaterial constructs. Stimulus-triggered approaches have been used to fabricate scaffolds with high resolution. Both features are useful to produce biomaterials that mimic the hierarchical organization of human tissues. Recently, multitechnology biofabrication approaches have been introduced that integrate benefits from different AM techniques to enable more complex materials design. However, few methods allow for tunable properties at both micro- and macro-scale in materials that are conducive for cell growth. To improve the organization of biofabricated constructs, we integrated direct ink writing (DIW) with digital light processing (DLP) to form multimaterial constructs with improved spatial control over final scaffold mechanics. Polymer–nanoparticle hydrogels were combined with methacryloyl gelatin (GelMA) to engineer dual inks that were compatible with both DIW and DLP. The shear-thinning and self-healing properties of the dual inks enabled extrusion-based 3D printing. The inclusion of GelMA provided a handle for spatiotemporal control of cross-linking with DLP. Exploiting this technique, complex multimaterial constructs were printed with defined mechanical reinforcement. In addition, the multitechnology approach was used to print live cells for biofabrication applications. Overall, the combination of DIW and DLP is a simple and efficient strategy to fabricate hierarchical biomaterials with user-defined control over material properties at both micro- and macro-scale.
Highlights
Additive manufacturing (AM) and biofabrication are increasingly leveraged in biomedical engineering to fabricate biological constructs with complex three-dimensional (3D) organization that mimic the structure and function of native tissues [1, 2]. 3D-printed constructs are applied as disease models to better understand pathology, as reproducible microtissues to screen or test new therapeutics, or directly as devices to repair or regenerate tissues [3,4,5,6,7,8]
Hydrogel formulation for combined Direct ink writing (DIW) and digital light processing (DLP) In this work, we combined DIW and DLP to fabricate scaffolds with hierarchical control over biomaterial composition and mechanical properties. This approach required dual bioinks that allowed for both DIW and DLP in a single material
In addition to having rheological properties for DIW, we demonstrated the ability for the dual bioinks to undergo secondary photo-cross-linking to replicate the process of photopatterning with DLP
Summary
Additive manufacturing (AM) and biofabrication are increasingly leveraged in biomedical engineering to fabricate biological constructs with complex three-dimensional (3D) organization that mimic the structure and function of native tissues [1, 2]. 3D-printed constructs are applied as disease models to better understand pathology, as reproducible microtissues to screen or test new therapeutics, or directly as devices to repair or regenerate tissues [3,4,5,6,7,8]. Direct ink writing (DIW) is a common biofabrication technique that builds 3D objects by depositing one or multiple biomaterials at specific locations via robotic dispensing [1, 9, 10]. DIW often requires biomaterial inks with suitable rheology to enable low pressure extrusion and shape retention [14]. Hydrogel-based inks with shear-thinning and self-healing properties are used to reduce shear-stresses during extrusion and increase shape retention post-fabrication. Smaller diameter nozzles result in increased shear stress and compromised viability [15, 16]. Because of this constraint, the resolution of deposition-based biofabrication remains one of its main limitations
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